The storage and periodic release of urine is controlled from several levels of the central nervous system, including the lumbosacral spinal cord, rostral pons, hypothalamus, numerous subcortical nuclei, and the cerebral cortex. Various evidence indicates that the excitatory parasympathetic component of the micturition reflex is dependent upon a supraspinal pathway originating in the rostral pons and sending fibers to the sacral spinal cord. Damage to the central nervous system caudal to this pontine area causes profound urinary retention. Clinical studies have also shown that damage to supropointine structures whether due to stroke, tumors, trama, or disease of the central nervous system can cause in some instances a huperactive bladder with urgency and incontinence and in other instances a hypoactive bladder with urinary retention. The studies outlined in the present proposal are designed to provide a detailed analysis, using modern neuroanatomical and neurophysiological techniques, of suprapontine structures which modulate the neuronal activity of the micturition reflex pathway. The aims of this proposed research are: (1) to identify site in the central nervous system using horseradish peroxidase tracting techniques which provide direct input to pontine micturition center (PMC) (2) to identify possible neurotransmitters which mediate the input to the PMC; enkephalins, serotonin, norepinephrine, substanace P and aaetylcholine will be of particular interest (3) to record evoked potentials from the PMC to pelvic nerve stimulation and examine the modulatory effects of stimulation of various forebrain structure (4) to block with specific neurotransmitter antogonists or mimic with agonists the modulatory influences mentioned above (5) to examine single neurons of the PMC using five barelled mocroelectrodes and to determine the effects of drugs applied iontophoretically to these neurons. The information gained in this study will not only provide a much more complete wiring diagram for the micturition pathway but may also suggest possible pharmacological modifications of the act of micturition.